In the following discussion certain articles and processes will be described for background and introductory purposes. Nothing contained herein is to be construed as an “admission” of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and processes referenced herein do not constitute prior art under the applicable statutory provisions.
The ability to detect the presence or absence of biomolecules in samples from a patient has enabled risk assessment for a variety of medical conditions, ranging from infectious disease to cancers to fetal abnormalities. The ability to determine more accurate risk assessments not only identifies the likelihood of various health conditions, in many cases it aids in informing decisions on potential therapeutic approaches and/or interventional techniques. However, in general non-invasive, conventional mechanisms for detecting biomolecules lack desired sensitivity and specificity and typically detect only one type of molecule at a time.
For example, biomolecules are detected in current prenatal screening tests to indicate a likelihood of fetal abnormalities, including Down Syndrome. AFP is a protein secreted by the fetal liver and excreted in the mother's blood, and a low level of AFP could also indicate Down Syndrome. The triple screen measures not only AFP, but beta-hCG and unconjugated estriol (uE3) as well, and the quadruple screen measures these three markers as well as inhibin A.
Although the use of additional markers increases the accuracy of the screening, even the combined biomolecule screening tests have issues. The detection rate for Down Syndrome is estimated to be 59% using the double test (AFP and hCG), 69% using the triple test (AFP, hCG, uE3), and 76% using the quadruple test (AFP, hCG, uE3, inhibin A), all in combination with maternal age. Wald N J et al., J Med Screen 1997 4:181-246. The tests used to confirm a positive screening result (e.g., amniocentesis or chorionic villus sampling) are invasive and carry up to a 1% rate of miscarriage of otherwise healthy, normal fetuses.
Enhanced methods to determine biomolecule levels associated with risk probabilities for various medical conditions are thus needed. (Note: For support for these amendments, please see the abstract.)